We have purified 4 mucous glycoprotein (MG) components secreted by intact and cultured human nasal and tracheobronchial epithelium. These components appear to differ largely in sulfate, and to a lesser extent, in sialic acid content. They are secreted more rapidly in vitro in response to cholinomimetic agents and theophyllin. Proposed studies are designed to elucidate the structure of MGP components, to relate composition and structure to the viscoelastic properties of these components and to better understand regulation of their secretion. MGP components will be fractionated further to identify subcomponents and microheterogeneity. Purified glycoprotein component, glycopeptides, and oligosaccharide sidechains will be subjected to amino acid, carbohydrate (glc), and sulfate analyses, structural studies of the glycoprotein components and their purified degradation products will be carried out by identifying (1) blood group, virus hemagglutination inhibition and multiple lectin specificities, (2) carbohydrate sequence and linkages by methylation and sequential reaction with glycosidases, (3) specific sulfated sugars released by partial acid hydrolysis and (4) carbohydrate-protein linkages. Microtechniques will be developed to measure the rheological properties of whole secretions and purified MGP components in order to determine quantitative relationships between structure and rheologic properties. The cholinergic mechanism for stimulation of secretion by explants will be explored further. Other potential secretagogues or inhibitors will be screened for an effect on human respiratory epithelium. All studies will be carried out on secretions or explants from patients with cystic fibrosis in an attempt to identify a chemical, rheologic, or regulatory abnormality which may be a pathogenetic factor in the obstructive lung disease of these patients.